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Background: Increasing the quantity and detail of bacteriophage genomic data is critical to broadening our understanding of how bacteriophages operate to allow us to harness their unique properties for biotechnology advancements. In this study we present the complete sequence of phage SV76's assembled and annotated genome (Accession No. OM339528). SV76 has previously been classified as a T4-like bacteriophage belonging to the Tequatrovirus genus within the Myoviridae family of contractile tailed bacteriophages. Materials and Methods: Whole genome sequencing, assembly, and annotation were performed on SV76. Double-agar spot assays were utilized to determine SV76's host range against a panel of 72 Escherichia coli isolates meant to represent the diversity of E. coli, as well as a series of knockouts designed to identify required receptor binding proteins. The genome and host range were compared with the closely related phage, T2. Results: Spot assays revealed that SV76 could plaque on 10 of the 72 strains (13.9%) and nine of the nine E. coli K12 single gene knockout of known phage receptors (100%). SV76 did not plate on a ΔfadL E. coli suggesting a requirement as a receptor binding protein. Conclusions: SV76 is closely related to T2 with similar host ranges within ECOR. This study presents novel host range and genomic data on SV76 phage, providing a foundation for future studies to further characterize SV76 to understand more about SV76 and other T4-like phages that can be applied to create novel biotechnologies.

Obesity and its sequelae have a major impact on human health. The stomach contributes to obesity in ways that extend beyond its role in digestion, including through effects on the microbiome. Gastrokine-1 (GKN1) is an anti-amyloidogenic protein abundantly and specifically secreted into the stomach lumen. We examined whether GKN1 plays a role in the development of obesity and regulation of the gut microbiome. Gkn1−/− mice were resistant to diet-induced obesity and hepatic steatosis (high fat diet (HFD) fat mass (g) = 10.4 ± 3.0 (WT) versus 2.9 ± 2.3 (Gkn1−/−) p −/−) p −/− mice also exhibited increased expression of the lipid-regulating hormone ANGPTL4 in the small bowel. The microbiome of Gkn1−/− mice exhibited reduced populations of microbes implicated in obesity, namely Firmicutes of the class Erysipelotrichia. Altered metabolism consistent with use of fat as an energy source was evident in Gkn1−/− mice during the sleep period. GKN1 may contribute to the effects of the stomach on the microbiome and obesity. Inhibition of GKN1 may be a means to prevent obesity.

Bacteriophages are viruses whose ubiquity in nature and remarkable specificity to their host bacteria enable an impressive and growing field of tunable biotechnologies in agriculture and public health. Bacteriophage capsids, which house and protect their nucleic acids, have been modified with a range of functionalities (e.g., fluorophores, nanoparticles, antigens, drugs) to suit their final application. Functional groups naturally present on bacteriophage capsids can be used for electrostatic adsorption or bioconjugation, but their impermanence and poor specificity can lead to inconsistencies in coverage and function. To overcome these limitations, researchers have explored both genetic and chemical modifications to enable strong, specific bonds between phage capsids and their target conjugates. Genetic modification methods involve introducing genes for alternative amino acids, peptides, or protein sequences into either the bacteriophage genomes or capsid genes on host plasmids to facilitate recombinant phage generation. Chemical modification methods rely on reacting functional groups present on the capsid with activated conjugates under the appropriate solution pH and salt conditions. This review surveys the current state-of-the-art in both genetic and chemical bacteriophage capsid modification methodologies, identifies major strengths and weaknesses of methods, and discusses areas of research needed to propel bacteriophage technology in development of biosensors, vaccines, therapeutics, and nanocarriers.

Light leaf spot, caused by the ascomycete Pyrenopeziza brassicae, is an established disease of Brassicaceae in the United Kingdom (UK), continental Europe, and Oceania (OC, including New Zealand and Australia). The disease was reported in North America (NA) for the first time in 2014 on Brassica spp. in the Willamette Valley of western Oregon, followed by detection in Brassica juncea cover crops and on Brassica rapa weeds in northwestern Washington in 2016. Preliminary DNA sequence data and field observations suggest that isolates of the pathogen present in NA might be distinct from those in the UK, continental Europe, and OC. Comparisons of isolates from these regions using genetic (multilocus sequence analysis, MAT gene sequences, and rep-PCR DNA fingerprinting), pathogenic (B. rapa inoculation studies), biological (sexual compatibility), and morphological (colony and conidial morphology) analyses demonstrated two genetically distinct evolutionary lineages. Lineage 1 comprised isolates from the UK, continental Europe, and OC, and included the P. brassicae type specimen. Lineage 2 contained the NA isolates associated with recent disease outbreaks in the Pacific Northwest region of the USA. Symptoms caused by isolates of the two lineages on B. rapa and B. juncea differed, and therefore "chlorotic leaf spot" is proposed for the disease caused by Lineage 2 isolates of P. brassicae. Isolates of the two lineages differed in genetic diversity as well as sensitivity to the fungicides carbendazim and prothioconazole.

Phage-based biosensors have shown significant promise in meeting the present needs of the food and agricultural industries due to a combination of sufficient portability, speed, ease of use, sensitivity, and low production cost. Although current phage-based methods do not meet the bacteria detection limit imposed by the EPA, FDA, and USDA, a better understanding of phage genetics can significantly increase their sensitivity as biosensors. In the current study, the signal sensitivity of a T4 phage-based detection system was improved via transcriptional upregulation of the reporter enzyme Nanoluc luciferase (Nluc). An efficient platform to evaluate the promoter activity of reporter T4 phages was developed. The ability to upregulate Nluc within T4 phages was evaluated using 15 native T4 promoters. Data indicates a six-fold increase in reporter enzyme signal from integration of the selected promoters. Collectively, this work demonstrates that fine tuning the expression of reporter enzymes such as Nluc through optimization of transcription can significantly reduce the limits of detection.

State-of-the-art Hg1−xCdxTe multilayer structures grown by molecular beam epitaxy on (211)-oriented Cd1−yZnyTe substrates have been characterized and their strain and relaxation analyzed. Techniques for measuring lattice mismatch, strain, and crystal quality by measuring symmetric and asymmetric diffraction profiles in different azimuths were adapted and performed in combination with dislocation delineation for full-wafer and multilayer characterization. It was found that the degree of lattice mismatch and in turn the strain state of epitaxial multilayers can be made uniform across full wafers in optimized structures. A strong correlation was revealed between the Zn composition of the Cd1−yZnyTe substrates and the crystal quality of the active layers in the multilayer structures. This method can be generalized to optimize multilayer structures to minimize relaxation by the generation of extended defects.

BackgroundVasovagal syncope (VVS) is the most common form of syncope, accounting for 50-60% of unexplained syncope. Currently diagnosis is achieved via clinical assessment combined with the Head-Up Tilt Test (HUT).AimTo examine the utility of the active stand test (AS) to identify those with a positive HUT or diagnosis of VVS.DesignRetrospective study of hemodynamic responses to AS.MethodsContinuous blood pressure responses to AS from 101 patients attending a Falls and Blackouts Unit were acquired, including: 37 controls (CON), 64 with a clinical diagnosis of VVS (VVS+) (34 tilt-positive (HUT+) and 30 tilt-negative (HUT-)) with a mean age of 25 ± 9 years. A total of 33 hemodynamic features were extracted with a subset of these entered into linear discriminant classifier. Classification accuracy was assessed using N-fold cross-validation.ResultsResults indicated that it was possible to classify the outcome of the HUT with sensitivity of 58.8%, specificity of 63.3% and an accuracy of 60.9%. Using a multivariate classifier it was possible to identify those with a positive diagnosis of VVS with a sensitivity of 84.3%, specificity of 72.9% and an accuracy of 80.2%.ConclusionThis study highlights the existence of a unique AS hemodynamic response characterised by autonomic hypersensitivity exhibited by young patients prone to VVS which is detectable using a multi-parameter machine learning framework. With further verification, this approach may have applications in syncope and falls diagnosis, population studies and the tracking of treatment efficacy.

A major limitation hindering the widespread use of synthetic phages in medical and industrial settings is the lack of an efficient phage-engineering platform. Classical T4 phage engineering and several newly proposed methods are often inefficient and time consuming and consequently, only able to produce an inconsistent range of genomic editing rates between 0.03–3%. Here, we review and present new understandings of the CRISPR/Cas9 assisted genome engineering technique that significantly improves the genomic editing rate of T4 phages. Our results indicate that crRNAs selection is a major rate limiting factor in T4 phage engineering via CRISPR/Cas9. We were able to achieve an editing rate of > 99% for multiple genes that functionalizes the phages for further applications. We envision that this improved phage-engineering platform will accelerate the fields of individualized phage therapy, biocontrol, and rapid diagnostics.

Phage-based biosensors have shown significant promise in meeting the present needs of the food and agricultural industries due to a combination of sufficient portability, speed, ease of use, sensitivity, and low production cost. Although current phage-based methods do not meet the bacteria detection limit imposed by the EPA, FDA, and USDA, a better understanding of phage genetics can significantly increase their sensitivity as biosensors. In the current study, the signal sensitivity of a T4 phage-based detection system was improved via transcriptional upregulation of the reporter enzyme Nanoluc luciferase (Nluc). An efficient platform to evaluate the promoter activity of reporter T4 phages was developed. The ability to upregulate Nluc within T4 phages was evaluated using 15 native T4 promoters. Data indicates a six-fold increase in reporter enzyme signal from integration of the selected promoters. Collectively, this work demonstrates that fine tuning the expression of reporter enzymes such as Nluc through optimization of transcription can significantly reduce the limits of detection.

Lipedema (LI) is a common yet misdiagnosed condition, often misconstrued with obesity. LI affects women almost exclusively, and its painful and life-changing symptoms have long been thought to be resistant to the lifestyle interventions such as diet and exercise. In this paper, we discuss possible mechanisms by which patients adopting a ketogenic diet (KD) can alleviate many of the unwanted clinical features of LI. This paper is also an effort to provide evidence for the hypothesis of the potency of this dietary intervention for addressing the symptoms of LI. Specifically, we examine the scientific evidence of effectiveness of adopting a KD by patients to alleviate clinical features associated with LI, including excessive and disproportionate lower body adipose tissue (AT) deposition, pain, and reduction in quality of life (QoL). We also explore several clinical features of LI currently under debate, including the potential existence and nature of edema, metabolic and hormonal dysfunction, inflammation, and fibrosis. The effectiveness of a KD on addressing clinical features of LI has been demonstrated in human studies, and shows promise as an intervention for LI. We hope this paper leads to an improved understanding of optimal nutritional management for patients with LI and stimulates future research in this area of study.

In this work, impurity ‘hot spot’ macro-defects—high impurity level macro-defect contaminates were examined. ‘Hot spots’ have very high localized concentrations of: K, Mg, Ni, Cr, Mn, Ca, Al, Na, Fe, and Cu. For example, these ‘hot spot’ macro-defects can have Cu concentrations > 1 × 1018 cm−3. Focused ion beam scanning transmission electron microscopy analysis of four ‘hot spots’ was performed. The origin of ‘hot spot’ defects is unresolved—however, our analysis has shown ‘hot spots’ can arise due to molecular beam epitaxy spit defects and CdZnTe substrate defects. The estimated ‘hot spot’ density is ∼ 30 cm−2. The presence of impurity ‘hot spot’ macro-defects in HgCdTe/CdZnTe is confirming evidence for the occurrence of L. Bubulac’s impurity ‘pipe’ mechanism.

Mercury cadmium telluride (HgCdTe, or MCT) with low n-type indium doping concentration offers a means for obtaining high performance infrared detectors. Characterizing carrier transport in materials with ultra low doping (ND = 1014 cm−3 and lower), and multi-layer material structures designed for infrared detector devices, is particularly challenging using traditional methods. In this work, Hall effect measurements with a swept B-field were used in conjunction with a multi-carrier fitting procedure and Fourier-domain mobility spectrum analysis to analyze multi-layered MCT samples. Low temperature measurements (77 K) were able to identify multiple carrier species, including an epitaxial layer (x = 0.2195) with n-type carrier concentration of n = 1 × 1014 cm−3 and electron mobility of μ = 280000 cm2/Vs. The extracted electron mobility matches or exceeds prior empirical models for MCT, illustrating the outstanding material quality achievable using current epitaxial growth methods, and motivating further study to revisit previously published material parameters for MCT carrier transport. The high material quality is further demonstrated via observation of the quantum Hall effect at low temperature (5 K and below).

Ultra-low-doped mercury cadmium telluride (HgCdTe, or MCT) is of significant interest for infrared detectors designed to suppress Auger recombination. Measurement of low doping levels in multi-layered structures is difficult with traditional 4-point Hall effect measurements. Multi-layered Hg.79Cd.21Te samples were analyzed using variable magnetic field Hall effect measurements and a multi-carrier fitting procedure. The measurements resolve two distinct carrier species corresponding to surface and/or buffer layer conduction and conduction through the primary low-doped material. High-quality electronic transport is achieved, including the demonstration of an epitaxial layer (x = 0.2195) with n = 1.09 × 1014 cm−3 and μ = 275,000 cm2/Vs at 77 K. This technique shows promise as a way to analyze layers with significantly lower doping, and a starting point to understand and advance the development of HgCdTe epilayers with very low doping concentration.

Light leaf spot, caused by the ascomycete Pyrenopeziza brassicae, is an established disease of Brassicaceae in the United Kingdom (UK), continental Europe, and Oceania (OC, including New Zealand and Australia). The disease was reported in North America (NA) for the first time in 2014 on Brassica spp. in the Willamette Valley of western Oregon, followed by detection in Brassica juncea cover crops and on Brassica rapa weeds in northwestern Washington in 2016. Preliminary DNA sequence data and field observations suggest that isolates of the pathogen present in NA might be distinct from those in the UK, continental Europe, and OC. Comparisons of isolates from these regions using genetic (multilocus sequence analysis, MAT gene sequences, and rep‐PCR DNA fingerprinting), pathogenic (B. rapa inoculation studies), biological (sexual compatibility), and morphological (colony and conidial morphology) analyses demonstrated two genetically distinct evolutionary lineages. Lineage 1 comprised isolates from the UK, continental Europe, and OC, and included the P. brassicae type specimen. Lineage 2 contained the NA isolates associated with recent disease outbreaks in the Pacific Northwest region of the USA. Symptoms caused by isolates of the two lineages on B. rapa and B. juncea differed, and therefore “chlorotic leaf spot” is proposed for the disease caused by Lineage 2 isolates of P. brassicae. Isolates of the two lineages differed in genetic diversity as well as sensitivity to the fungicides carbendazim and prothioconazole., Pyrenopeziza brassicae was first found on Brassica spp. in North America (NA) in 2014. The consolidated species concept showed NA isolates are in a distinct evolutionary lineage compared to isolates from continental Europe and the UK.

Background Theoretically, two types of emotional responding could underlie individual differences in trait affect: 1) a disposition reflecting increased probability of experiencing positive or negative emotions (emotional reactivity), and 2) a disposition to experience prolonged emotional reactions once elicited (emotional perseveration). We developed a measure of these dimensions and investigated whether emotional reactivity and perseveration 1) account for unique variance in trait affect, and 2) are differentially associated with symptoms of psychological distress. Method In Study 1, participants (T1: n = 90; T2: n = 51) completed the Positive and Negative Affect Schedule (PANAS) and the Emotional Reactivity and Perseveration Scale (ERPS, adapted from the PANAS). In study 2, participants ( n = 228) completed the PANAS, ERPS, and Depression Anxiety Stress Scales. Results Study 1 established the basic psychometric properties of the ERPS and demonstrated that emotional reactivity and perseveration accounted for unique variance in trait positive and negative effect. Study 2 confirmed these findings and established that emotional reactivity and perseveration are differentially associated with depression, anxiety, and stress scores. Conclusion Emotional reactivity and perseveration represent independent dimensions of trait affect. Considering these dimension in future research could further the understanding of both normal emotional responding and emotional vulnerability.

We review recent advances in the HgCdTe material quality and detector performance achieved at Teledyne using molecular beam epitaxy growth and the double-layer planar hetero-junction (DLPH) detector architecture. By using an un-doped, fully depleted absorber, Teledyne’s DLPH architecture can be extended for use in high operating temperatures and other applications. We assess the potential achievable performance for long wavelength infrared (LWIR) hetero-junction p-lightly-doped n or p-intrinsic-n (p-i-n) detectors based on recently reported results for 10.7 μm cutoff 1 K × 1 K focal plane arrays (FPAs) tested at temperatures down to 30 K. Variable temperature dark current measurements show that any Shockley–Read–Hall currents in the depletion region of these devices have lifetimes that are reproducibly greater than 100 ms. Under the assumption of comparable lifetimes at higher temperatures, it is predicted that fully-depleted background radiation-limited performance can be expected for 10-μm cutoff detectors from room temperature to well below liquid nitrogen temperatures, with room-temperature dark current nearly 400 times lower than predicted by Rule 07. The hetero-junction p-i-n diode is shown to have numerous other significant potential advantages including minimal or no passivation requirements for pBn-like processing, low 1/f noise, compatibility with small pixel pitch while maintaining high modulation transfer function, low crosstalk and good quantum efficiency. By appropriate design of the FPA dewar shielding, analysis shows that dark current can theoretically be further reduced below the thermal equilibrium radiative limit. Modeling shows that background radiation-limited LWIR HgCdTe operating with f/1 optics has the potential to operate within √2 of background-limited performance at 215 K. By reducing the background radiation by 2/3 using novel shielding methods, operation with a single-stage thermo-electric-cooler may be possible. If the background radiation can be reduced by 90%, then room-temperature operation is possible.

Background Grape phylloxera (Daktulosphaira vitifoliae Fitch) is a major insect pest that negatively impacts commercial grapevine performance worldwide. Consequently, the use of phylloxera resistant rootstocks is an essential component of vineyard management. However, the majority of commercially available rootstocks used in viticulture production provide limited levels of grape phylloxera resistance, in part due to the adaptation of phylloxera biotypes to different Vitis species. Therefore, there is pressing need to develop new rootstocks better adapted to specific grape growing regions with complete resistance to grape phylloxera biotypes. Results Grapevine rootstock breeding material, including an accession of Vitis cinerea and V. aestivalis, DRX55 ([M. rotundifolia x V. vinifera] x open pollinated) and MS27-31 (M. rotundifolia specific hybrid), provided complete resistance to grape phylloxera in potted plant assays. To map the genetic factor(s) of grape phylloxera resistance, a F1 V. cinerea x V. vinifera Riesling population was screened for resistance. Heritability analysis indicates that the V. cinerea accession contained a single allele referred as RESISTANCE TO DAKTULOSPHAIRA VITIFOLIAE 2 (RDV2) that confers grape phylloxera resistance. Using genetic maps constructed with pseudo-testcross markers for V. cinerea and Riesling, a single phylloxera resistance locus was identified in V. cinerea. After validating SNPs at the RDV2 locus, interval and linkage mapping showed that grape phylloxera resistance mapped to linkage group 14 at position 16.7 cM. Conclusion The mapping of RDV2 and the validation of markers linked to grape phylloxera resistance provides the basis to breed new rootstocks via marker-assisted selection that improve vineyard performance. Electronic supplementary material The online version of this article (10.1186/s12870-018-1590-0) contains supplementary material, which is available to authorized users.

State-of-the-art as-received (112)B CdZnTe substrates were examined for surface impurity contamination, polishing damage, and tellurium precipitates/inclusions. A maximum surface impurity concentration of Al = 7.5 × 1014, Si = 3.7 × 1013, Cl = 3.12 × 1015, S = 1.7 × 1014, P = 7.1 × 1013, Fe = 1.0 × 1013, Br = 1.9 × 1012, and Cu = 4 × 1012 atoms cm−2 was observed on an as-received 6 × 6 cm wafer. As-received CdZnTe substrates have scratches and residual polishing grit on the (112)B surface. Polishing scratches are 0.3 nm in depth and 0.1 μm wide. The polishing grit density was observed to vary from wafer-to-wafer from ∼5 × 106 to 2 × 108 cm−2. Te precipitate/inclusion size and density was determined by near-infrared automated microscopy. A Te precipitate/inclusion diameter histogram was obtained for the near-surface (top ~140 μm) of a 6 × 6 cm substrate. The average areal Te precipitate/inclusion density was observed to be fairly uniform. However, there was a large density of Te precipitates/inclusions with a diameter significantly greater than the mean. Te precipitate/inclusion density >10 μm diameter = 2.8 × 103 cm−3. The large Te precipitates/inclusions are laterally non-uniformly distributed across the wafer.

Operators for deepwater and extended-reach wells, where daily rig costs can exceed $500k per day, are continuously exploring methods to reduce nonproductive time (NPT) and increase operational efficiency. One particular area of interest is the deployment of liner strings, which are commonly used as an alternative to long casing strings to minimize well construction costs and increase drilling efficiency. For deepwater and highly deviated applications, hydraulic liner hangers are predominantly used over mechanical tools due to the limitations of pipe manipulation needed to set the hanger. The traditional method for setting a hydraulic liner hanger includes the use of one or more activation balls dropped from surface so that pressure can be applied to the workstring to function the hydraulic liner hanger and running tool. However, in deepwater and extended-reach applications, the time to pump or gravitate the ball on seat can take up to 3 hours. In addition, there are many cases where the ball never properly lands on seat, which can lead to days of more NPT. Developing a liner hanger system that does not rely on dropping activation balls from surface, nor rely on pipe manipulation can reduce the time required to run the liner hanger and minimize issues that lead to increased NPT. This paper presents how a new liner hanger system was developed to use simple mud flow signals to remotely communicate with a downhole controller located on the workstring. The downhole controller receives the specific activation signal from surface and then relays that signal to the liner hanger or running tool via an acoustic signal. The liner hanger and running tool are then actuated with an electronically triggered hydrostatic actuator. This new system does not require dropping activation balls from surface, simplifying system hook-up and reducing the amount of time required to set the liner hanger. The system also allows a solid liner hanger body with no pressure ports, eliminating the potential leak paths inherent to hydraulic liner hangers. The novel approach to design and develop the remote liner hanger system to minimize operational risks and reduce development time will be discussed in detail. This includes the evolution of the remote system from field-proven hydraulic liner hanger technology and the results from testing performed to qualify the remote communication methodology. This liner hanger system improves well construction efficiencies and is a step in the direction of a smarter and safer oilfield through more automated operations.

Operators for deepwater and extended-reach wells, where daily rig costs can exceed $500k per day, are continuously exploring methods to reduce nonproductive time (NPT) and increase operational efficiency. For example, a common point of focus is liner string deployments in deepwater and highly deviated applications that predominantly employ hydraulic liner hangers. This paper presents a new liner hanger system that uses simple mud flow signals to remotely communicate with a downhole controller on the work string. The controller receives the specific activation signal from the surface and then relays that signal to the liner hanger or running tool via an acoustic signal. The results of the first test trial of the remote liner hanger system controller will be discussed. The traditional method for setting a hydraulic liner hanger includes the use of single or multiple activation balls being dropped from the surface so that pressure can be applied to the work string to function the hydraulic liner hanger and running tool. However, in deepwater and extended-reach applications, many operational issues experienced with running hydraulic liner hangers are related to not landing the ball on seat, which can lead to days of NPT. Developing a liner hanger system that does not rely on dropping activation balls from the surface nor rely on pipe manipulation can reduce the time required to run the liner hanger and minimize issues that lead to higher NPT. This new system does not require dropping activation balls from the surface, reducing the amount of running tools in the work string and the amount of time required to set the liner hanger. The system also allows the use of a solid liner hanger body, eliminating the potential leak paths inherent to hydraulic liner hangers. The results will demonstrate the first deployment of the remote system controller in a well, confirming that it detects various remote commands from the surface. The results will also demonstrate how the system enables operators to choose the activation method depending on the well and rig conditions, for example, varying the flow rate activation signals. This system and method can improve well construction efficiencies and is a step in the direction of a smarter and safer oilfield through more automated operations.

State-of-the-art (112)B CdZnTe substrates were examined for near-surface tellurium precipitate-related defects. The Te precipitate density was observed to be fairly uniform throughout the bulk of the wafer, including the near-surface region. After a molecular beam epitaxy (MBE) preparation etch, exposed Te precipitates, small pits, and bumps on the (112)B surface of the CdZnTe wafer were observed. From near-infrared and dark field microscopy, the bumps and small pits on the CdZnTe surface are associated with strings of Te precipitates. Raised bumps are Te precipitates near the surface of the (112)B CdZnTe where the MBE preparation etch has not yet exposed the Te precipitate(s). An exposed Te precipitate sticking above the etched CdZnTe surface plane occurs when the MBE preparation etch rapidly undercuts a Te precipitate. Shallow surface pits are formed when the Te precipitate is completely undercut from the surrounding (112)B surface plane. The Te precipitate that was previously located at the center of the pit is liberated by the MBE preparation etch process.

IgA nephropathy is described in 11 cases out of a total of 177 renal biopsies examined representing an incidence of 6.2 per cent.Reference is made to comparable studies from other centres. Clinical and pathological findings are presented and discussed.

HgCdTe, because of its narrow band gap and low dark current, is the infrared detector material of choice for several military and commercial applications. CdZnTe is the substrate of choice for HgCdTe as it can be lattice matched, resulting in low-defect-density epitaxy. Being often small and not circular, layers grown on CdZnTe are difficult to process in standard semiconductor equipment. Furthermore, CdZnTe can often be very expensive. Alternate inexpensive large circular substrates, such as silicon or gallium arsenide, are needed to scale HgCdTe detector production. Growth of HgCdTe on these alternate substrates has its own difficulty, namely large lattice mismatch (19% for Si and 14% for GaAs). This large mismatch results in high defect density and reduced detector performance. In this paper we discuss ways to reduce the effects of dislocations by gettering these defects to the edge of a reticulated structure. These reticulated surfaces enable stress-free regions for dislocations to glide to. In this work, a novel structure was developed that allows for etch pit density of less than 4 × 105/cm2 for HgCdTe-on-Si. This is almost two orders of magnitude less than the as-grown etch pit density of 1.1 × 107/cm2. This value of 3.35 × 105/cm2 is below the

Alternate substrates for molecular beam epitaxy growth of HgCdTe including Si, Ge, and GaAs have been under development for more than a decade. MBE growth of HgCdTe on GaAs substrates was pioneered by Teledyne Imaging Sensors (TIS) in the 1980s. However, recent improvements in the layer crystal quality including improvements in both the CdTe buffer layer and the HgCdTe layer growth have resulted in GaAs emerging as a strong candidate for replacement of bulk CdZnTe substrates for certain infrared imaging applications. In this paper the current state of the art in CdTe and HgCdTe MBE growth on (211)B GaAs and (211) Si at TIS is reviewed. Recent improvements in the CdTe buffer layer quality (double crystal rocking curve full-width at half-maximum ≈ 30 arcsec) with HgCdTe dislocation densities of ≤106 cm−2 are discussed and comparisons are made with historical HgCdTe on bulk CdZnTe and alternate substrate data at TIS. Material properties including the HgCdTe majority carrier mobility and dislocation density are presented as a function of the CdTe buffer layer quality.

HgCdTe, because of its narrow band gap and low dark current, is the infrared detector material of choice for several military and commercial applications. CdZnTe is the substrate of choice for HgCdTe as it can be lattice matched, resulting in low-defect-density epitaxy. Being often small and not circular, layers grown on CdZnTe are difficult to process in standard semiconductor equipment. Furthermore, CdZnTe can often be very expensive. Alternative inexpensive large circular substrates, such as silicon or gallium arsenide, are needed to scale production of HgCdTe detectors. Growth of HgCdTe on these alternative substrates has its own difficulty, namely a large lattice mismatch (19% for Si and 14% for GaAs). This large mismatch results in high defect density and reduced detector performance. In this paper we discuss ways to reduce the effects of dislocations by gettering these defects to the edge of a reticulated structure. These reticulated surfaces enable stress-free regions for dislocations to glide to. In the work described herein, HgCdTe-on-Si diodes have been produced with R0A0 of over 400 Ω cm2 at 78 K and cutoff of 10.1 μm. Further, these diodes have good uniformity at 78 K at both 9.3 μm and 10.14 μm.

A model is proposed to explain disparities found in the operability values and histograms for long-wavelength infrared HgCdTe focal-plane arrays fabricated on Si substrates compared with those fabricated on CdZnTe. The starting point for the model is the close agreement between the aerial density of discrete species (particles, contamination spots, crystalline defects on Si surface) in various interfaces in the HgCdTe/CdTe/Si structure and the density of failed pixels in the array. The density of discrete species is acquired by applying a newly developed variation of the secondary-ion mass spectrometry (SIMS) depth-profiling technique to samples that have been deuterated to enhance detection. A mechanism of selective activation of threading dislocations in a HgCdTe layer on Si is proposed to link discrete species with failed detector pixels.

Arrays of x-ray microcalorimeters will enable broadband, high-resolution x-ray spectroscopy to study and substantiate black holes, dark matter, and other celestial phenomenon. At EPIR we continue to achieve growth of high-quality, low-doped, single-crystal HgCdTe, and HgTe epilayers on Si and CdZnTe to be employed by NASA in these instruments. Excellent low-temperature heat capacities (with no significant electronic term) have been demonstrated in integrated devices, with both HgTe and HgCdTe showing improvement over the HgTe used previously. Goal resolutions ≤4 eV have been achieved with good yield for both HgTe and HgCdTe.

Single-crystalline CdTe(133) films have been grown by metalorganic chemical vapor deposition on Si(211) substrates. We studied the effect of various growth parameters on the surface morphology and structural quality of CdTe films. Proper oxide removal from the Si substrate is considered to be the principal factor that influences both the morphology and epitaxial quality of the CdTe films. In order to obtain single-crystalline CdTe(133) films, a two-stage growth method was used, i.e., a low-temperature buffer layer step and a high- temperature growth step. Even when the low-temperature buffer layer shows polycrystalline structure, the overgrown layer shows single-crystalline structure. During the subsequent high-temperature growth, two-dimensional crystallites grow faster than other, randomly distributed crystallites in the buffer layer. This is because the capturing of adatoms by steps occurs more easily due to increased adatom mobility. From the viewpoint of crystallographic orientation, it is assumed that the surface structure of Si(211) consists of (111) terrace and (100) step planes with an interplanar angle of 54.8°. This surface structure may provide many preferable nucleation sites for adatoms compared with nominally flat Si(100) or (111) surfaces. The surface morphology of the resulting films shows macroscopic rectangular-shaped terrace—step structures that are considered to be a (111) terrace with two {112} step planes directed toward 〈110〉.

Pleiotrophin (PTN) is a heparin-binding protein with multiple activities in cell growth, migration and differentiation mediated through multiple receptors. In mammals, PTN expression in trophoblast is found exclusively in the human and in some of the apes in which an endogenous retrovirus upstream of the first coding exon generates a phylogenetically new trophoblast-specific promoter associated with exon UV3. To understand the functions of ERV promoter-mediated trophoblastic PTN expression in pregnancy, we correlated the expression of PTN and its receptors anaplastic lymphoma kinase (ALK), receptor protein tyrosine phosphatase beta/zeta (RPTPbeta/zeta), and Syndecan-1 and Syndecan-3 (SDC1 and SDC3) with key developmental processes in first-trimester human placentation. In an extensive survey of cell lines and primary tissues, we found that trophoblastic transcription of PTN is initiated exclusively from the ERV promoter, whereas decidual expression is initiated at the phylogenetically ancient U1 exon-associated promoter. Using immunohistochemistry, we found that different patterns of overlapping expression of PTN and its receptors occur in different trophoblast subtypes. Notably, a role in angiogenesis is supported by expression of PTN and its receptors in villous mesenchyme, fetal macrophages and villus core fetal vessels. PTN staining of extravillous cytotrophoblasts and the syncytial microvillous membrane is consistent with increasing levels of PTN, as measured by ELISA, in the maternal bloodstream as pregnancy progresses.

The use of silicon as an alternative substrate to bulk CdZnTe for epitaxial growth of HgCdTe for infrared detector applications is attractive because of potential cost savings as a result of the large available sizes and the relatively low cost of silicon substrates. However, the potential benefits of silicon as a substrate have been difficult to realize because of the technical challenges of growing low-defect-density HgCdTe on silicon where the lattice mismatch is ∼19%. This is especially true for long-wavelength infrared (LWIR) HgCdTe detectors where the performance can be limited by the high (∼5 × 106 cm−2) dislocation density typically found in HgCdTe grown on silicon. The current status of LWIR (9 μm to 11 μm at 78 K) HgCdTe on silicon focal-plane arrays (FPAs) is reviewed. Recent progress is covered including improvements in noise equivalent differential temperature (NEDT) and array operability. NEDT of 99% are highlighted for 640 × 480 pixel, 20-μm-pitch FPAs.

Reverse current in diodes can be dominated by generation processes, depending exponentially on temperature according to the rate-limiting step in the generation process. In this report, the current-voltage-temperature (IVT) relationship is analyzed for several midwave infrared and long-wave infrared (MWIR x = 0.295, LWIR x = 0.233) Hg1−x Cd x Te (MCT) diodes. The energy varied from diode to diode. At high reverse biases, the energy tends toward the band gap energy. Close to zero bias, the energy ranged from 0.06 to 0.1 eV. Deep level transient spectroscopy (DLTS) showed a broad peak centered at 55–80 K for the MWIR MCT. Comparison of the DLTS spectrum to a simulation based on the energy and capture cross section from a rate window analysis shows that the peak is a band of traps. The capacitance transient amplitude increased as the filling pulse increased from 1 µs to 0.1 s, consistent with capture at a dislocation. A shift to lower temperatures for the peak was also observed when the diodes are cooled under forward bias. The shift is reversible, indicating that the traps consist at least partially of a bistable defect.

It has been reported that the basic electrical properties of n-type long wave length infrared (LWIR) HgCdTe grown on silicon, including the majority carrier mobility (μ e) and minority carrier lifetime (τ), are qualitatively comparable to those reported for LWIR HgCdTe grown on bulk CdZnTe by molecular beam epitaxy (MBE). Detailed measurements of the majority carrier mobility have revealed important differences between the values measured for HgCdTe grown on bulk CdZnTe and those measured for HgCdTe grown on buffered silicon substrates. The mobility of LWIR HgCdTe grown on buffered silicon by MBE is reported over a large temperature range and is analyzed in terms of standard electron scattering mechanisms. The role of dislocation scattering is addressed for high dislocation density HgCdTe grown on lattice-mismatched silicon. Differences between the low temperature mobility data of HgCdTe grown on bulk CdZnTe and HgCdTe grown on silicon are partially explained in terms of the dislocation scattering contribution to the total mobility.

The as-grown molecular beam epitaxy (MBE) (211)B HgCdTe surface has variable surface topography, which is primarily dependent on substrate temperature and substrate/epilayer mismatch. Nano-ripple formation and cross-hatch patterning are the predominant structural features observed. Nano-ripples preferentially form parallel to the \( [\bar {1}11] \) and are from 0 A to 100 A in height with a wavelength between 0.1 μm and 0.8 μm. Cross-hatch patterns result from slip dislocations in the three {111} planes intersecting the (211) growth surface. The cross-hatch step height is 4 ± 1 A (limited data set). This indicates that only a bi-layer slip (Hg/Cd + Te) in the {111} slip plane occurs. For the deposition of MBE (211)B HgCdTe/CdTe/Si, the reorientation of multiple nano-ripples coalesced into “packets” forms cross-hatch patterns. The as-grown MBE (211)B CdTe/Si surface is highly variable but displays nano-ripples and no cross-hatch pattern. Three types of defects were observed by atomic force microscopy (AFM): needle, void/hillock, and voids.

Preliminary results of a study of the hydrogenation of HgCdTe epilayers grown by molecular beam epitaxy on Si substrates using a glow-discharge plasma are presented. The aim of the program is to employ H to passivate the detrimental opto-electronic effects of threading dislocations present in the HgCdTe epilayers. Secondary ion mass spectroscopy depth profiling has been performed to characterize 1H and 2H incorporation. It has been found that H can be controllably incorporated in HgCdTe epilayers to levels in the 1014 cm−3 to 1018 cm−3 range while maintaining the sample at temperatures lower than 60°C. Profiles indicate that H accumulates in regions of known high defect density or in highly strained regions. Analysis of the H depth profile data indicates that the current density-time product is a good figure of merit to predict the H levels in the HgCdTe epilayer. There are progressive differences in the 1H and 2H uptake efficiencies as a function of depth. Magneto-Hall measurements show consistently higher mobilities at low temperatures for majority carriers in hydrogenated samples.

We have fabricated a series of 256 pixel×256 pixel, 40 µm pitch LWIR focal plane arrays (FPAs) with HgCdTe grown on (211) silicon substrates using MBE grown CdTe and CdSeTe buffer layers. The detector arrays were fabricated using Rockwell Scientific’s double layer planar heterostructure (DLPH) diode architecture. The 78 K detector and focal plane array (FPA) performance are discussed in terms of quantum efficiency (QE), diode dark current and dark current operability. The FPA dark current and the tail in the FPA dark current operability histograms are discussed in terms of the HgCdTe epitaxial layer defect density and the dislocation density of the individual diode junctions. Individual diode zero bias impedance and reverse bias current-voltage (I-V) characteristics vs. temperature are discussed in terms of the dislocation density of the epitaxial layer, and the misfit stress in the epitaxial multilayer structure, and the thermal expansion mismatch in the composite substrate. The fundamental FPA performance limitations and possible FPA performance improvements are discussed in terms of basic device physics and material properties.

The use of silicon as a substrate alternative to bulk CdZnTe for epitaxial growth of HgCdTe for infrared (IR) detector applications is attractive because of potential cost savings as a result of the large available sizes and the relatively low cost of silicon substrates. However, the potential benefits of silicon as a substrate have been difficult to realize because of the technical challenges of growing low defect density HgCdTe on silicon where the lattice mismatch is ∼19%. This is especially true for LWIR HgCdTe detectors where the performance can be limited by the high (∼5×106 cm−2) dislocation density typically found in HgCdTe grown on silicon. We have fabricated a series of long wavelength infrared (LWIR) HgCdTe diodes and several LWIR focal plane arrays (FPAs) with HgCdTe grown on silicon substrates using MBE grown CdTe and CdSeTe buffer layers. The detector arrays were fabricated using Rockwell Scientific’s planar diode architecture. The diode and FPA and results at 78 K will be discussed in terms of the high dislocation density (∼5×106 cm2) typically measured when HgCdTe is grown on silicon substrates.

This paper reports the further development of the model for the analysis of FTIR transmission spectra from the dual-color Hg1−xCdxTe (MCT) structures for the constituent layer thickness and alloy composition. The previously reported model1 was shown to suffer from excessively high uncertainty in the provided individual layer thickness and low convergence rate for some types of structures, attributed primarily to inaccuracies in the model representation of the MCT dielectric function. Since last report, we have substantially improved the FTIR analysis accuracy by developing a better MCT dielectric function approximation, which is based on the interpolation of the measured spectroscopic ellipsometry (SE) experimental spectral dielectric functions at few discrete alloy compositions. Based on this, the optical model for graded layers was also created and calibrated against the traditional FTIR data reduction technique. The new model was shown to produce the most accurate fits to the experimental FTIR transmission spectra from single- and two-color detector structures, and has demonstrated a better convergence rate. The new model was tested to predict both band cutoff wavelengths for the actual two-color MWIR/LWIR SUMIT detectors.15 We have demonstrated that the model prediction from as-grown structures was in good agreement with the actual two-color device data, as measured on performance evaluation chips (PECs), thus validating the modeling technique for routine postgrowth wafer screening.

In the past several years, we have made significant progress in the growth of CdTe buffer layers on Si wafers using molecular beam epitaxy (MBE) as well as the growth of HgCdTe onto this substrate as an alternative to the growth of HgCdTe on bulk CdZnTe wafers. These developments have focused primarily on mid-wavelength infrared (MWIR) HgCdTe and have led to successful demonstrations of high-performance 1024×1024 focal plane arrays (FPAs) using Rockwell Scientific’s double-layer planar heterostructure (DLPH) architecture. We are currently attempting to extend the HgCdTe-on-Si technology to the long wavelength infrared (LWIR) and very long wavelength infrared (VLWIR) regimes. This is made difficult because the large lattice-parameter mismatch between Si and CdTe/HgCdTe results in a high density of threading dislocations (typically, >5E6 cm−2), and these dislocations act as conductive pathways for tunneling currents that reduce the RoA and increase the dark current of the diodes. To assess the current state of the LWIR art, we fabricated a set of test diodes from LWIR HgCdTe grown on Si. Silicon wafers with either CdTe or CdSeTe buffer layers were used. Test results at both 78 K and 40 K are presented and discussed in terms of threading dislocation density. Diode characteristics are compared with LWIR HgCdTe grown on bulk CdZnTe.

The reproducible molecular-beam epitaxy (MBE) growth of dual-band Hg1−xCdxTe (MCT) heterostructures requires routine post-growth wafer analysis for constituent layer thickness and alloy composition, therefore, demanding nondestructive characterization techniques that offer quick data feedback. This paper reports a multilayer structure model, which can be least-square fit directly to either Fourier transform infrared (FTIR) transmission or reflection spectra to provide individual layer thickness, alloy composition, and grading information for various complex structures. The model, we developed, is based on an accurate representation of both the real and imaginary parts of the MCT dielectric function across and above Eg as a function of alloy composition. The parametric, MCT optical-dielectric function for compositions varying between x=0.17 to x=0.5 was developed in the range from 400 cm−1 to 4,000 cm−1, based on a semi-empirical model for the absorption coefficient and extrapolation of the refractive index across Eg. The model parameters were refined through simultaneous fits to multiple reflection and transmission data sets from as-grown, double-layer planar heterostructure (DLPH) structures of variable thickness. The multilayer model was tested on a variety of simple DLPH structures with thick absorber layers (>8 µm) and was compared against traditional FTIR analysis and cross-section optical microscopy and showed good agreement in both composition and thickness. Model fits to dual-color MCT data and subsequent analysis of the internal parameter correlation have demonstrated that error bars on absorber layer composition and thickness could be as low as ∼0.0005 and ∼0.02 µm, correspondingly.

A study of optical absorption in HgCdTe layers is presented to provide an improved model for the absorption coefficient. Measurements were performed on samples grown by molecular beam epitaxy using automated compositional control from spectroscopic ellipsometry measurements. Several samples with varying alloy composition and layer thickness were measured at varying temperatures to build an absorption model to represent bandtail and above bandgap absorption. Best-fit parameters for the optical absorption coefficient model are presented as a function of temperature and composition and are compared to previously published models. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Lattice mismatch between the substrate and the absorber layer in single-color HgCdTe infrared (IR) detectors and between band 1 and band 2 in two-color detectors results in the formation of crosshatch lines on the surface and an array of misfit dislocations at the epi-interfaces. Threading dislocations originating in the substrate can also bend into the interface plane and result in misfit dislocations because of the lattice mismatch. The existence of dislocations threading through the junction region of HgCdTe IR-photovoltaic detectors can greatly affect device performance. High-quality CdZnTe substrates and controlled molecular-beam epitaxy (MBE) growth of HgCdTe can result in very low threading-dislocation densities as measured by the etch-pit density (EPD ∼ 104cm−2). However, dislocation gettering to regions of high stress (such as etched holes, voids, and implanted-junction regions) at elevated-processing temperatures can result in a high density of dislocations in the junction region that can greatly reduce detector performance. We have performed experiments to determine if the dislocations that getter to these regions of high stress are misfit dislocations at the substrate/absorber interface that have a threading component extending to the upper surface of the epilayer, or if the dislocations originate at the cap/absorber interface as misfit dislocations. The preceding mechanisms for dislocation motion are discussed in detail, and the possible diode-performance consequences are explored.